[Development and evaluation of the simplified Chinese versions of motion sickness susceptibility questionnaire].

Objective: To develop and evaluate the simplified Chinese versions of motion sickness susceptibility questionnaire (MSSQ)-long (MSSQ-L) and MSSQ-short (MSSQ-S). Methods: A cross-sectional study was conducted in May 2023 among 3 426 university students at North China University of Science and Technology. The Chinese versions of MSSQ-L and MSSQ-S were distributed, and item selection for Simplified Chinese versions of MSSQ-L and MSSQ-S was performed based on item response rates, item-total correlations, Cronbach's alpha coefficients, and standard deviations. Forty-five male and forty-five female participants were recruited from the initial survey population to complete Coriolis acceleration endurance testing and fill out the simplified Chinese versions of MSSQ-L and MSSQ-S, and Graybiel symptom severity score questionnaire. Internal consistency, external consistency, criterion validity, discriminant validity, and predictive accuracy for motion sickness severity were assessed. Results: A total of 3 111 valid responses were received for the Chinese versions of MSSQ, yielding an effective response rate of 90.8% (3 111/3 426). Among the 3 111 students surveyed, there were 965 males and 2 146 females, with a mean age of (19.5±1.4) years. The highest usage rates for item were observed for cars (98.9%, 3 077/3 111) and buses (98.8%, 3 073/3 111). The simplified Chinese versions of MSSQ-L and MSSQ-S consisted of four and eight items, respectively. The Cronbach's alpha coefficients were 0.900 and 0.953 for the simplified Chinese versions of MSSQ-S and MSSQ-L, respectively, with test-retest reliabilities of 0.895 and 0.908. Criterion validity coefficients were 0.814 and 0.765 for the simplified Chinese versions of MSSQ-S and MSSQ-L, respectively. In terms of discriminant validity, significant differences were observed between mild and moderate susceptibility groups [0(0, 3) vs 6(2, 10), P=0.006] and between moderate and severe susceptibility groups [6(2, 10) vs 9(6, 13), P=0.030] for the simplified Chinese version of MSSQ-S. Significant differences were also observed between mild and moderate susceptibility groups [5(0, 3) vs 7(3, 10), P=0.001], but not between moderate and severe susceptibility groups [7(3, 10) vs 7(3, 10), P=0.081] for simplified Chinese version of MSSQ-L. The overall predictive accuracy for motion sickness severity improved from 55.6% (50/90) to 62.2% (56/90) for the simplified Chinese version of MSSQ-S and from 54.4% (49/90) to 58.9% (53/90) for the simplified Chinese version of MSSQ-L, but with no statistically significant differences (both P>0.05). Conclusions: The simplified Chinese versions of MSSQ-L and MSSQ-S demonstrates good reliability and validity. The simplified Chinese version of MSSQ-S exhibits satisfactory discriminant validity, and can serve as a simple and efficient tool for assessing motion sickness susceptibility.

[Effects of tumor location and mismatch repair on clinicopathological features and survival for non-metastatic colon cancer: A retrospective, single center, cohort study].

Objective: To analyze the differences in clinicopathological features of colon cancers and survival between patients with right- versus left-sided colon cancers. Methods: This was a retrospective cohort study. Information on patients with colon cancer from January 2016 to August 2020 was collected from the prospective registry database at Peking Union Medical College Hospital . Primary tumors located in the cecum, ascending colon, and proximal two-thirds of the transverse colon were defined as right-sided colon cancers (RCCs), whereas primary tumors located in the distal third of the transverse colon, descending colon, or sigmoid colon were defined as left-sided colon cancers (LCCs). Clinicopathological features were compared using the χ2 test or Mann-Whitney U test. Survival was estimated by Kaplan-Meier curves and the log-rank test. Factors that differed significantly between the two groups were identified by multivariate survival analyses performed with the Cox proportional hazards function. One propensity score matching was performed to eliminate the effects of confounding factors. Results: The study cohort comprised 856 patients, with TNM Stage I disease, 391 (45.7%) with Stage II, and 336 (39.3%) with Stage III, including 442 (51.6%) with LCC and 414 (48.4%) with RCC and 129 (15.1%). Defective mismatch repair (dMMR) was identified in 139 patients (16.2%). Compared with RCC, the proportion of men (274/442 [62.0%] vs. 224/414 [54.1%], χ2=5.462, P=0.019), body mass index (24.2 [21.9, 26.6] kg/m2 vs. 23.2 [21.3, 25.5] kg/m2, U=78,789.0, P<0.001), and well/moderately differentiated cancer (412/442 [93.2%] vs. 344/414 [83.1%], χ2=22.266, P<0.001) were higher in the LCC than the RCC group. In contrast, the proportion of dMMR (40/442 [9.0%] vs. 99/414 [23.9%], χ2=34.721, P<0.001) and combined vascular invasion (106/442[24.0%] vs. 125/414[30.2%], χ2=4.186, P=0.041) were lower in the LCC than RCC group. The median follow-up time for all patients was 48 (range 33, 59) months. The log-rank test revealed no significant differences in disease-free survival (DFS) (P=0.668) or overall survival (OS) (P=0.828) between patients with LCC versus RCC. Cox proportional hazards model showed that dMMR was significantly associated with a longer DFS (HR=0.419, 95%CI: 0.204‒0.862, P=0.018), whereas a higher proportion of T3-4 (HR=2.178, 95%CI: 1.089‒4.359, P=0.028), N+ (HR=2.126, 95%CI: 1.443‒3.133, P<0.001), and perineural invasion (HR=1.835, 95%CI: 1.115‒3.020, P=0.017) were associated with poor DFS. Tumor location was not associated with DFS or OS (all P>0.05). Subsequent analysis showed that RCC patients with dMMR had longer DFS than did RCC patients with pMMR (HR=0.338, 95%CI: 0.146‒0.786, P=0.012). However, the difference in OS between the two groups was not statistically significant (HR=0.340, 95%CI:0.103‒1.119, P=0.076). After propensity score matching for independent risk factors for DFS, the log-rank test revealed no significant differences in DFS (P=0.343) or OS (P=0.658) between patients with LCC versus RCC, whereas patient with dMMR had better DFS (P=0.047) and OS (P=0.040) than did patients with pMMR. Conclusions: Tumor location is associated with differences in clinicopathological features; however, this has no impact on survival. dMMR status is significantly associated with longer survival: this association may be stronger in RCC patients.

Dose-Painting Proton Radiotherapy Guided by Functional MRI in Non-enhancing High-Grade Gliomas.

AIMS: This study aimed to demonstrate the feasibility and evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). MATERIALS AND METHODS: The 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)-(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). RESULTS: Compared with the IMRT plan, the D2 and D50 of the PRT plans with the same prescription dose increased by 1.27-4.12% and 0.64-2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve >98% TCP for PRT, and it was 84Gy to achieve >91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. CONCLUSION: The functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.

Genome-wide association analysis of eggshell color of an F2 generation population reveals candidate genes in chickens.

Eggshell color is an important visual characteristic that affects consumer preferences for eggs. Eggshell color, which has moderate to high heritability, can be effectively enhanced through molecular marker selection. Various studies have been conducted on eggshell color at specific time points. However, few longitudinal data are available on eggshell color. Therefore, the objective of this study was to investigate eggshell color using the Commission International de L'Eclairage L*a*b* system with multiple measurements at different ages (age at the first egg and at 32, 36, 40, 44, 48, 52, 56, 60, 66, and 72 weeks) within the same individuals from an F2 resource population produced by crossing White Leghorn and Dongxiang Blue chicken. Using an Affymetrix 600 single nucleotide polymorphism (SNP) array, we estimated the genetic parameters of the eggshell color trait, performed genome-wide association studies (GWASs), and screened for the potential candidate genes. The results showed that pink-shelled eggs displayed a significant negative correlation between L* values and both a* and b* values. Genetic heritability based on SNPs showed that the heritability of L*, a*, and b* values ranged from 0.32 to 0.82 for pink-shelled eggs, indicating a moderate to high level of genetic control. The genetic correlations at each time point were mostly above 0.5. The major-effect regions affecting the pink eggshell color were identified in the 10.3-13.0 Mb interval on Gallus gallus chromosome 20, and candidate genes were selected, including SLC35C2, PCIF1, and SLC12A5. Minor effect polygenic regions were identified on chromosomes 1, 6, 9, 12, and 15, revealing 11 candidate genes, including MTMR3 and SLC35E4. Members of the solute carrier family play an important role in influencing eggshell color. Overall, our findings provide valuable insights into the phenotypic and genetic aspects underlying the variation in eggshell color. Using GWAS analysis, we identified multiple quantitative trait loci (QTLs) for pink eggshell color, including a major QTL on chromosome 20. Genetic variants associated with eggshell color may be used in genomic breeding programs.

HYPOXIA induces lncRNA HOTAIR for recruiting RELA in papillary thyroid cancer cells to upregulate miR-181a and promote angiogenesis.

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the most common subtypes of thyroid carcinoma. Exosomal miR-181a plays an important role in the development of PTC. This study examined the regulatory mechanism of miR-181a under conditions of hypoxia and its impact on angiogenesis. METHODS: A ribonucleoprotein immunoprecipitation (RIP) experiment was conducted to verify the interaction between HOTAIR and RELA. The relationship between RELA and the miR-181a promoter was detected by ChIP-qPCR. Short hairpin (sh) RNA was designed to knock down HOTAIR in TPC cells. The underlying mechanism of miR-181a was verified by use of dual-luciferase assays and rescue experiments. The regulatory effect of GATA6 on angiogenesis was studied using CCK8, EdU, Transwell, and western blot assays. RESULTS: A RIP assay showed that HOTAIR could bind to RELA under hypoxic conditions. ChIP-qPCR and dual luciferase assays showed RELA could interact with the miR181a promoter and upregulate miR-181a. Knockdown of HOTAIR downregulated miR-181a in TPC-1 cells, and the downregulation could be rescued by RELA overexpression. MiR-181a downregulated GATA6 in HUVEC cells. Overexpression of GATA6 inhibited HUVEC proliferation, migration, tube formation, and EGFR expression. Exosomal miR-181a promoted angiogenesis by downregulating GATA6 expression. CONCLUSION: HOTAIR activated RELA to upregulate miR-181a during hypoxia. Exosomal miR-181a promotes tumor angiogenesis by downregulating GATA6.

[Investigation on the cognitive level of Mpox among MSM population in Shenzhen and analysis of the influencing factors in 2023].

From June 16 to 30, 2023, men who have sex with men (MSM) who had visited Voluntary Counseling Testing (VCT) clinics in the Luohu, Futian and Nanshan districts of Shenzhen were included in this study to analyze their awareness of Mpox and the influencing factors. The mean age of the 262 MSM was (34.78±8.94) years, with the majority being unmarried (75.2%) and 79.0% confirmed to be infected with HIV. The awareness rates for five primary indicators, current status of Mpox, pathogen and source of infection, mode of transmission, population susceptibility, clinical manifestations and treatment were 68.4%, 84.7%, 60.3%, 87.8%, and 52.5%, respectively. The awareness rates for five secondary indicators, earliest transmission location (44.7%), main mode of transmission (54.2%), role of masks (46.9%), drug accessibility (46.6%), and self-limiting nature (38.2%) were all below 60%. The MSM population in Shenzhen perceived their likelihood of being infected (2.76±1.32) and discriminated against (3.87±1.26) as relatively low. The logistic analysis showed that the high school or vocational school education (OR:3.094, 95%CI:1.180-9.299), college or above education (OR:5.360, 95%CI:2.159-15.501), and higher scores on questions affecting learning or work (OR:2.196, 95%CI:1.409-3.599) were promoting factors for Mpox awareness, while higher scores on questions concerning the possibility of Mpox mortality (OR:0.591, 95%CI:0.432-0.791) was the hindering factor for Mpox awareness.

New primers for sex identification in the Chukar partridges (Alectoris chukar).

1. Male and female Chukar partridges are difficult to differentiate based on their morphology or by the Chromobox-Helicase-DNA binding (CHD) during early growth.2. The current study developed a novel, simple, low-cost and rapid sexing protocol for Chukar partridges based on the newly defined sexing gene ubiquitin-associated protein 2 (UBAP2).3. The length of polymorphism between UBAP2-W and UBAP2-Z homologous genes allows for easy sex discrimination in this species. Molecular sexing analysis was based on the simultaneous amplification of both genes, resulting in two distinct amplicons (947 bp and 535 bp) in heterogametic females and only a single band (535 bp) in homogametic males, which is easy to detect with agarose gel electrophoresis.4. This technique is simple and convenient for genetic sex determination in Chukar partridges.

The complexity of glucose time series is associated with short- and long-term mortality in critically ill adults: a multi-center, prospective, observational study.

BACKGROUND: The wealth of data taken from continuous glucose monitoring (CGM) remains to be fully used. We aimed to evaluate the relationship between a promising new CGM metric, complexity of glucose time series index (CGI), and mortality in critically ill patients. METHODS: A total of 293 patients admitted to mixed medical/surgical intensive care units from 5 medical centers in Shanghai were prospectively included between May 2020 and November 2021. CGI was assessed using intermittently scanned CGM, with a median monitoring period of 12.0 days. Outcome measures included short- and long-term mortality. RESULTS: During a median follow-up period of 1.7 years, a total of 139 (47.4%) deaths were identified, of which 73 (24.9%) occurred within the first 30 days after ICU admission, and 103 (35.2%) within 90 days. The multivariable-adjusted HRs for 30-day mortality across ascending tertiles of CGI were 1.00 (reference), 0.68 (95% CI 0.38-1.22) and 0.36 (95% CI 0.19-0.70), respectively. For per 1-SD increase in CGI, the risk of 30-day mortality was decreased by 51% (HR 0.49, 95% CI 0.35-0.69). Further adjustment for HbA1c, mean glucose during hospitalization and glucose variability partially attenuated these associations, although the link between CGI and 30-day mortality remained significant (per 1-SD increase: HR 0.57, 95% CI 0.40-0.83). Similar results were observed when 90-day mortality was considered as the outcome. Furthermore, CGI was also significantly and independently associated with long-term mortality (per 1-SD increase: HR 0.77, 95% CI 0.61-0.97). CONCLUSIONS: In critically ill patients, CGI is significantly associated with short- and long-term mortality.

[Estrogen, estrogen receptor and miR-21 in adenomyosis: their pathogenic roles and regulatory interactions].

OBJECTIVE: To explore the pathogenic roles of miR-21, estrogen (E2), and estrogen receptor (ER) in adenomyosis. METHODS: We examined the expression levels of miR-21 in specimens of adenomyotic tissue and benign cervical lesions using qRT-PCR. In primary cultures of cells isolated from the adenomyosis lesions, the effect of ICI82780 (an ER inhibitor) on miR-21 expression levels prior to E2 activation or after E2 deprivation were examined with qRT-PCR. We further assessed the effects of a miR-21 mimic or an inhibitor on proliferation, apoptosis, migration and autophagy of the cells. RESULTS: The expression level of miR-21 was significantly higher in adenomyosis tissues than in normal myometrium (P < 0.05). In the cells isolated from adenomyosis lesions, miR-21 expression level was significantly higher in E2 activation group than in ER inhibition + E2 activation group and the control group (P < 0.05); miR-21 expression level was significantly lower in cells in E2 deprivation+ER inhibition group than in E2 deprivation group and the control group (P < 0.05). The adenomyosis cells transfected with miR-21 inhibitor showed inhibited proliferation and migration, expansion of mitochondrial endoplasmic reticulum, increased lysosomes, presence of autophagosomes, and increased cell apoptosis, while transfection of the cells with the miR-21 mimic produced the opposite effects. CONCLUSION: MiR-21 plays an important role in promoting proliferation, migration, and antiapoptosis in adenomyosis cells by altering the cell ultrastructure, which may contribute to early pathogenesis of the disease. In addition to binding with E2, ER can also regulate miR-21 through other pathways to participate in the pathogenesis of adenomyosis, thus having a stronger regulatory effect on miR-21 than E2.

[Jisuikang formula promotes spinal cord injury repair in rats by activating the YAP/PKM2 signaling axis in astrocytes].

OBJECTIVE: To investigate the effect of Jisuikang formula-medicated serum for promoting spinal cord injury (SCI) repair in rats and explore the possible mechanism. METHODS: Thirty adult SD rats were randomized into sham-operated group, SCI (induced using a modified Allen method) model group, and Jisuikang formula-medicated serum treatment group. After the operations, the rats were treated with normal saline or Jisuikang by gavage on a daily basis for 14 days, and the changes in hindlimb motor function of the rats was assessed with Basso-Beattie-Bresnahan (BBB) scores and inclined-plate test. The injured spinal cord tissues were sampled from the SCI rat models for single-cell RNA sequencing, and bioinformatics analysis was performed to identify the target genes of Jisuikang, spinal cord injury and glycolysis. In the cell experiment, cultured astrocytes from neonatal SD rat cortex were treated with SOX2 alone or in combination with Jisuikang-medicated serum for 21 days, and the protein expressions of PKM2, p-PKM2 and YAP and colocalization of PKM2 and YAP in the cells were analyzed with Western blotting and immunofluorescence staining, respectively. RESULTS: The SCI rats with Jisuikang treatment showed significantly improved BBB scores and performance in inclined-plate test. At the injury site, high PKM2 expression was detected in various cell types. Bioinformatic analysis identified the HIPPO-YAP signaling pathway as the target pathway of Jisuikang. In cultured astrocytes, SOX2 combined with the mediated serum, as compared with SOX2 alone, significantly increased PKM2, p-PKM2 and YAP expressions and entry of phosphorylated PKM2 into the nucleus, and promoted PKM2 and YAP co-localization in the cells. CONCLUSION: Jisuikang formula accelerates SCI repair in rats possibly by promoting aerobic glycolysis of the astrocytes via activating the PKM2/YAP axis to induce reprogramming of the astrocytes into neurons.

[Analysis of clinical manifestations and prognosis of primary systemic light chain amyloidosis with liver involvement].

Objective: To summarize the clinical manifestations and prognostic factors of patients with hepatic amyloidosis in a single center. Methods: The clinical data of 28 primary systemic light chain amyloidosis cases with liver involvement in our center from October 2012 to January 2023 were retrospectively analyzed. The main clinical manifestations and prognostic factors were studied. Statistical analysis were performed using the χ(2) test, Fisher's exact test, Wilcoxon rank test, or Kaplan-Meier survival curve log-rank test according to the different data. Results: The main clinical manifestations of patients with liver involvement were abdominal distension, hepatomegaly, and edema. CD56 and chemokine receptor 4 protein expression accounted for 52% (13/25) and 56% (14/25). 64.3% (9/14) patients were combined with t (11,14), and 21.4% (3/14) patients were positive for 1q21 (+), and no patients were detected with del(17p). Univariate analysis showed that Mayo 2004 and 2012 stages and total bilirubin (TBil) ≥34.2 µmol/L were associated with progression-free survival and overall survival. The median progression-free survival and overall survival were significantly inferior in patients with TBil≥34.2µmol/L group (0.178 years, 0.195 years) than with the TBil<34.2µmol/L group (0.750 years, 3.586 years) (P < 0.05). Conclusion: Mayo stage and hyperbilirubinemia are inferior prognostic factors for patients with primary systemic light chain amyloidosis accompanied with liver involvement.

Application of machine learning techniques in the diagnostic approach of PTSD using MRI neuroimaging data: A systematic review.

Background: At present, the diagnosis of post-traumatic stress disorder（PTSD） mainly relies on clinical symptoms and psychological scales, and finding objective indicators that are helpful for diagnosis has always been a challenge in clinical practice and academic research. Neuroimaging is a useful and powerful tool for discovering the biomarkers of PTSD,especially functional MRI (fMRI), structural MRI (sMRI) and Diffusion Weighted Imaging（DTI）are the most commonly used technologies, which can provide multiple perspectives on brain function, structure and its connectivity. Machine learning (ML) is an emerging and potentially powerful method, which has aroused people's interest because it is used together with neuroimaging data to define brain structural and functional abnormalities related to diseases, and identify phenotypes, such as helping physicians make early diagnosis. Objectives: According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) declaration, a systematic review was conducted to assess its accuracy in distinguishing between PTSD patients, TEHC(Trauma-Exposed Healthy Controls), and HC(healthy controls). Methods: We searched PubMed, Embase, and Web of Science using common words for ML methods and PTSD until June 2023, with no language or time limits. This review includes 13 studies, with sensitivity, specificity, and accuracy taken from each publication or acquired directly from the authors. Results: All ML techniques have an diagnostic accuracy rate above 70%，and support vector machine（SVM） are the most commonly used techniques. This series of studies has revealed significant neurobiological differences in key brain regions among individuals with PTSD, TEHC, and HC. The connectivity patterns of regions such as the Insula and Amygdala hold particular significance in distinguishing these groups. TEHC exhibits more normal connectivity patterns compared to PTSD, providing valuable insights for the application of machine learning in PTSD diagnosis. Conclusion: In contrast to any currently available assessment and clinical diagnosis, ML techniques can be used as an effective and non-invasive support for early identification and detection of patients as well as for early screening of high-risk populations.

[Construction and validation of an in-hospital mortality risk prediction model for patients receiving VA-ECMO: a retrospective multi-center case-control study].

OBJECTIVE: To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January, 2015 and January, 2022 using a convenience sampling method. The patients were divided into a derivation cohort (201 cases) and a validation cohort (101 cases). Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients, based on which a risk prediction model was established in the form of a nomogram. The receiver operator characteristic (ROC) curve, calibration curve and clinical decision curve were used to evaluate the discrimination ability, calibration and clinical validity of this model. RESULTS: The in-hospital mortality risk prediction model was established based the risk factors including hypertension (OR=3.694, 95% CI: 1.582-8.621), continuous renal replacement therapy (OR=9.661, 95%CI: 4.103-22.745), elevated Na2 + level (OR=1.048, 95% CI: 1.003-1.095) and increased hemoglobin level (OR=0.987, 95% CI: 0.977-0.998). In the derivation cohort, the area under the ROC curve (AUC) of this model was 0.829 (95% CI: 0.770-0.889), greater than those of the 4 single factors (all AUC < 0.800), APACHE II Score (AUC=0.777, 95% CI: 0.714-0.840) and the SOFA Score (AUC=0.721, 95% CI: 0.647-0.796). The results of internal validation showed that the AUC of the model was 0.774 (95% CI: 0.679-0.869), and the goodness of fit test showed a good fitting of this model (χ2=4.629, P>0.05). CONCLUSION: The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation, calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system, and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.

Nuclear RNA homeostasis promotes systems-level coordination of cell fate and senescence.

Understanding cellular coordination remains a challenge despite knowledge of individual pathways. The RNA exosome, targeting a wide range of RNA substrates, is often downregulated in cellular senescence. Utilizing an auxin-inducible system, we observed that RNA exosome depletion in embryonic stem cells significantly affects the transcriptome and proteome, causing pluripotency loss and pre-senescence onset. Mechanistically, exosome depletion triggers acute nuclear RNA aggregation, disrupting nuclear RNA-protein equilibrium. This disturbance limits nuclear protein availability and hinders polymerase initiation and engagement, reducing gene transcription. Concurrently, it promptly disrupts nucleolar transcription, ribosomal processes, and nuclear exporting, resulting in a translational shutdown. Prolonged exosome depletion induces nuclear structural changes resembling senescent cells, including aberrant chromatin compaction, chromocenter disassembly, and intensified heterochromatic foci. These effects suggest that the dynamic turnover of nuclear RNA orchestrates crosstalk between essential processes to optimize cellular function. Disruptions in nuclear RNA homeostasis result in systemic functional decline, altering the cell state and promoting senescence.

Effects of manganese glycine on eggshell quality, eggshell ultrastructure, and elemental deposition in aged laying hens.

Poor eggshell quality of eggs laid by aged laying hens is the major problem affecting the length of the rearing period in the laying hen industry. Trace elements are required and play vital roles in the eggshell quality of laying hens. Appropriate dose of organic microelements is environmentally friendly and sufficient to satisfy the needs of hens because of their greater bioavailability and lower excretion than inorganic forms. The aim of this experiment was to investigate the effects of manganese (Mn) glycine (MG) on eggshell quality, elemental deposition, and eggshell ultrastructure in aged laying hens. A total of 720 Hy-Line Brown hens 70 weeks old were assigned equally to four groups with six replicates of 30 birds each. The hens were fed basal diets (without Mn supplementation) supplemented with 120 mg/kg of Mn from manganese sulfate monohydrate (MSM), or 40, 80, or 120 mg/kg Mn from MG for 12 weeks. Dietary supplementation with 80 mg/kg Mn from MG resulted in the greatest eggshell strength after 6 weeks of treatment (P = 0.047), and in greater eggshell strength than observed in the MSM control after 12 weeks of treatment (P = 0.025). After 12 weeks of treatment, the eggs of hens in the MG groups showed lower mammillary layer thickness in the blunt end, equator, and acute end than observed in the MSM control group (P < 0.001). With the exception of the blunt ends of eggs from hens in the 120 mg/kg MG group, the eggs of hens in the MG groups, compared with the MSM control group, exhibited a lower mammillary layer ratio, and greater palisade layer ratio and effective layer ratio in the blunt end, equator, and acute end (P < 0.001). Dietary supplementation with 80 mg/kg Mn from MG, compared with the MSM control and 40 and 120 mg/kg MG, resulted in the greatest palisade layer thickness and effective layer thickness, and the lowest mammillary layer thickness in the equator (P < 0.001, P = 0.001, P < 0.001, respectively). Furthermore, supplementation with 80 mg/kg Mn from MG exhibited the greatest ratio of the palisade layer and effective layer, and the lowest mammillary layer ratio in the blunt end and equator (all P < 0.001). The Mn content of eggshells in hens-fed diets supplemented with 80 and 120 mg/kg Mn from MG was greater than that in the MSM control and 40 mg/kg MG groups (P = 0.035). Dietary supplementation with 80 or 120 mg/kg Mn from MG resulted in greater tibia Mn content than observed in the 40 mg/kg MG group (P = 0.019), and greater yolk Mn content than observed in the 40 mg/kg MG and MSM control groups (P = 0.018). In conclusion, dietary supplementation with 80 mg/kg Mn from MG, compared with the MSM control (120 mg/kg Mn), may increase the deposition efficiency of Mn, alter eggshell elemental composition, improve eggshell ultrastructure, and enhance eggshell strength in aged laying hens.

[Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection].

Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

[Current status and challenges of immunotherapy for multiple myeloma].

Multiple myeloma (MM) is the second most common hematologic malignancy and the incidence of MM in mainland China in 2016 was 1.15/100 000.With the development of China's aging society, the incidence of MM is expected to increase year by year. Immunotherapy for MM has become the fourth pillar of therapy after autologous hematopoietic stem cell transplantation, immunomodulators, and proteasome inhibitors, and is the most active area of MM treatment. Nine new drugs have been approved for multiple myeloma treatment in China, and three are expected to be approved in 2024, which will focus on immunotherapy. There are many ambiguities about the current status of research and utilization in this emerging field in China. Determining the optimal integration of these therapies into the treatment regimen for Chinese MM patients constitutes a critical challenge for clinicians. Immunotherapy for MM primarily encompasses two major categories: antibody-based drug therapy and cellular immunotherapy. Antibody-based medications primarily include monoclonal antibodies, T-cell engagers, IgG-like bispecific antibodies, and trispecific antibodies. Cellular immunotherapy mainly consists of chimeric antigen receptor T (CAR-T) cells, as well as other immune cells such as chimeric antigen receptor natural killer (CAR-NK) cells, dendritic cells, T cell receptor-engineered T cells, and peptide vaccines.This article mainly focuses on the current research status and existing issues of the aforementioned immunotherapy methods, with the aim of providing references for the treatment of MM.